The long range goal of the research supported by this grant is to identify electrophysiologically the central nervous system pathways that are involved in the control of cardiovascular function. During the current funding period we have used state- of-the-art electrophysiological analyses to identify major efferent and afferent connections of rostral ventrolateral medullary (VLM) neurons that likely account for their role in the control of sympathetic nerve discharge (SND) in the Dial-urethane anesthetized cat. The experiments described in this proposal extends the use of these techniques to studies of the hypothalamic paraventricular nucleus and dorsomedial hypothalamus (PVN- DMH) as well as the preoptic-anterior hypothalamic area (PO- AHA). These hypothalamic nuclei have recently received considerable attention as forebrain regions involved in the control of SND and blood pressure. PVN neurons project directly to the intermediolateral (IML) autonomic nucleus in the thoracolumbar spinal cords well as to brainstem autonomic regions (e.g., the nucleus tractus solitarius, the rostral VLM, the pontine locus coeruleus and parabrachial complex (LC/PB), and the mesencephalic periaqueductal gray (PAG)). PO-AHA neurons project to the PVN and to the LC/PB and PAG. Little information is currently available concerning the electrophysiological properties of PVN-DMH and PO-AHA neurons contained in these pathways. The brainstem regions innervated by PVN-DMH and PO-AHA neurons also provide input to these hypothalamic nuclei. Thus, feedback loops may play a role in controlling the activity within central sympathetic circuits. Recently, our laboratory has used the technique of spike-triggered averaging to identify two types of neurons in the PVN and PO- AHA whose spontaneous activity is correlated to that in the inferior cardiac sympathetic nerve in anesthetized cats. The spontaneous discharges of Type 1 neurons are synchronized to a spike-like component in inferior cardiac nerve activity, whereas the activity of Type 2 neurons is locked to the cardiac-related component in SND. It remains to be determined whether these hypothalamic neurons are involved in the control of resting SND. If both of these neuronal types control cardiovascular function, they probably do so by exerting their effects over different central pathways. The experiments outlined in this proposal are designed to determine which PVN-DMH and PO-AHA neurons are elements of efferent sympathetic (excitatory or inhibitory) pathways or interneurons in the afferent limb of the baroreceptor reflex arc. We also will be able to identify some of the major efferent and afferent connections of these neurons. The electrophysiological techniques to be used include spike-triggered averaging of SND, antidromic mapping and tests for axonal branching, and unit minus or greater than unit crosscorrelation analysis.